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New Nanosized Systems Doxorubicin-Amphiphilic Copolymers of N-Vinylpyrrolidone and (Di)methacrylates with Antitumor Activity.

ABSTRACT: Nanosized systems of DOX with antitumor activity on the base of micelle-like particles of amphiphilic thermosensitive copolymers of N-vinylpyrrolidone (VP) with triethylene glycol dimethacrylate (TEGDM), and N-vinylpyrrolidone and methacrylic acid (MAA) with TEGDM were explored. They were investigated in aqueous solutions by electron absorption spectroscopy, dynamic light scattering and cyclic voltammetry. Experimental data and quantum-chemical modeling indicated the formation of a hydrogen bond between oxygen-containing groups of monomer units of the copolymers and H-atoms of OH and NH₂ groups of DOX; the energies and H-bond lengths in the considered structures were calculated. A simulation of TDDFT spectra of DOX and its complexes with the VP and TEGDM units was carried out. Electrochemical studies in PBS have demonstrated that the oxidation of encapsulated DOX appeared to be easier than that of the free one, and its reduction was somewhat more difficult. The cytotoxicity of VP-TEGDM copolymer compositions containing 1, 5 and 15 wt% DOX was studied in vitro on HeLa cells, and the values of IC₅₀ doses were determined at 24 and 72 h of exposure. The copolymer compositions containing 5 and 15 wt% DOX accumulated actively in cell nuclei and did not cause visual changes in cell morphology.

SUBMITTER: Kurmaz SV

PROVIDER: S-EPMC9784683 | biostudies-literature | 2022 Nov

REPOSITORIES: biostudies-literature

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New Nanosized Systems Doxorubicin-Amphiphilic Copolymers of N-Vinylpyrrolidone and (Di)methacrylates with Antitumor Activity.

Kurmaz Svetlana V SV Ignatiev Vladislav M VM Emel'yanova Nina S NS Kurmaz Vladimir A VA Konev Dmitry V DV Balakina Anastasiya A AA Terentyev Alexey A AA

Pharmaceutics 20221123 12

Nanosized systems of DOX with antitumor activity on the base of micelle-like particles of amphiphilic thermosensitive copolymers of N-vinylpyrrolidone (VP) with triethylene glycol dimethacrylate (TEGDM), and N-vinylpyrrolidone and methacrylic acid (MAA) with TEGDM were explored. They were investigated in aqueous solutions by electron absorption spectroscopy, dynamic light scattering and cyclic voltammetry. Experimental data and quantum-chemical modeling indicated the formation of a ...[more]

PMID: 36559068

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Project description:BackgroundIn breast cancer (BC), tumor-associated macrophages (TAMs) are an important component of the tumor microenvironment and are closely related to poor prognosis. A growing number of studies have focused on the role of TAMs in BC progression and therapeutic strategies targeting TAMs. As an emerging treatment, the application of nanosized drug delivery systems (NDDSs) in the treatment of BC by targeting TAMs has attracted much attention.AimsThis review is to summarize the characteristics and treatment strategies targeting TAMs in BC and to clarify the applications of NDDSs targeting TAMs in the treatment of BC by targeting TAMs.Materials & methodsThe existing results related to characteristics of TAMs in BC, BC treatment strategies by targeting TAMs, and the applications of NDDSs in these strategies are described. Through analyzing these results, the advantages and disadvantages of the treatment strategies using NDDSs are discussed, which could provide advices on designing NDDSs for BC treatment.ResultsTAMs are one of the most prominent noncancer cell types in BC. TAMs not only promote angiogenesis, tumor growth and metastasis but also lead to therapeutic resistance and immunosuppression. Mainly four strategies have been used to target TAMs for BC therapy, which include depleting macrophages, blocking recruitment, reprogramming to attain an anti-tumor phenotype, and increasing phagocytosis. Since NDDSs can efficiently deliver drugs to TAMs with low toxicity, they are promising approaches for targeting TAMs in tumor therapy. NDDSs with various structures can deliver immunotherapeutic agents and nucleic acid therapeutics to TAMs. In addition, NDDSs can realize combination therapies.DiscussionTAMs play a critical role in the progression of BC. An increasing number of strategies have been proposed to regulate TAMs. Compared with free drugs, NDDSs targeting TAMs improve drug concentration, reduce toxicity and realize combination therapies. However, in order to achieve better therapeutic efficacy, there are still some disadvantages that need to be considered in the design of NDDSs.ConclusionTAMs play an important role in the progression of BC, and targeting TAMs is a promising strategy for BC therapy. In particular, NDDSs targeting TAMs have unique advantages and are potential treatments for BC.

Dataset Information

New Nanosized Systems Doxorubicin-Amphiphilic Copolymers of N-Vinylpyrrolidone and (Di)methacrylates with Antitumor Activity.

Publications

New Nanosized Systems Doxorubicin-Amphiphilic Copolymers of <i>N</i>-Vinylpyrrolidone and (Di)methacrylates with Antitumor Activity.

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